In this laboratory, a new protein which is antigenically similar to oxytocin (OT) and arginine vasotocin (AVT) has been found in human plasma and is termed "the novel OT-like peptide." This novel peptide rises in human plasma in response to administration of estrogen (acute and chronic); rises when endogenous levels of estrogen increase (mid-cycle and pregnancy); and is also found in high concentrations in the plasma of patients with chronic renal failure. This novel peptide has heretofore not been described in humans. Reverse phase HPLC separates this material from OT. Two peaks of immunoreactivity, one eluting before and one after OT, are found when plasma from individuals given estrogen, plasma from pregnant women, and plasma from patients with renal failure are chromatographed. All conditions in which the OT-like peptide have been increased have also been characterized by high levels of the estrogen-stimulated neurophysin (ESN), suggesting that ESN and the OT-like peptide are released together and perhaps synthesized and/or are stored together. The quantity of this material in human plasma is less than 10 pg/ml and the identity of this substance is dependent on isolating large amounts of the material. The quantity of plasma needed to recover 100 ng of a salt-free protein - the minimum required for amino acid analysis using the most sensitive of methods - would be in excess of 10 liters. Therefore, a body fluid (as urine from an individual given estrogen or pregnant women or the used dialysate from chronic renal failure patients) and/or a tissue source of the material are being sought and methods of extraction of the peptide, concentration of body fluid and tissue extracts, HPLC isolation and amino acid analysis form one focus of this grant. Because the peptide bears structural similarities to OT, concentrated extracts of the peptide will be tested for oxytocic activity by performing bio- and radioreceptor assays and the release of the OT-like peptide in response to stimuli known to promote release of oxytocin will be tested. By so doing we will learn whether the OT-like peptide and OT are regulated differentially or in parallel and in the process also learn more about the physiology of oxytocin, a hormone about which very little is known.